The research program in this laboratory aims at elucidating the structures and functions of cell membranes. One project is concerned with the biochemistry of animal cell surfaces in the normal and malignant state, while the other, the project described in this application, will attempt to provide a molecular description for solute transport across the cytoplasmic membrane. A bacterial phosphotransferase system previously isolated in this laboratory has been shown to be responsible for the group translocation of carbohydrates which are substrates of the system. The system is also involved in regulating the transport of other solutes across the membrane, in cell motility and chemotaxis, in maintaining intracellular concentrations of cyclic AMP, and in the synthesis of certain inducible catabolic enzymes. Emphasis will be placed on isolating homogeneous components of the phosphotransferase system, on studying their interaction with each other and membrane lipid, on reconstituting transport systems in synthetic lipid vesicles, on the physiological functions of each component of the system (using appropriate mutants), and on determining how they regulate the other processes listed above. Elucidation of the molecular mechanisms described above should permit a direct approach to understanding the abnormalities which occur in plasma membrane functions, such as those detected in cystic fibrosis, diabetes, etc.